Adenovirus dodecahedron, as a drug delivery vector
Bleomycin (BLM) is an anticancer antibiotic used in many cancer regimens. Its utility is limited by systemic toxicity and dose-dependent pneumonitis able to progress to lung fibrosis. The latter can affect up to nearly 50% of the total patient population, out of which 3% will die. We propose to impr...
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| description | Bleomycin (BLM) is an anticancer antibiotic used in many cancer regimens. Its utility is limited by systemic toxicity and dose-dependent pneumonitis able to progress to lung fibrosis. The latter can affect up to nearly 50% of the total patient population, out of which 3% will die. We propose to improve BLM delivery by tethering it to an efficient delivery vector. Adenovirus (Ad) dodecahedron base (DB) is a particulate vector composed of 12 copies of a pentameric viral protein responsible for virus penetration. The vector efficiently penetrates the plasma membrane, is liberated in the cytoplasm and has a propensity to concentrate around the nucleus; up to 300000 particles can be observed in one cell in vitro.
Dodecahedron (Dd) structure is preserved at up to about 50 degrees C at pH 7-8 and during dialysis, freezing and drying in the speed-vac in the presence of 150 mM ammonium sulfate, as well as during lyophilization in the presence of cryoprotectants. The vector is also stable in human serum for 2 h at 37 degrees C. We prepared a Dd-BLM conjugate which upon penetration induced death of transformed cells. Similarly to free bleomycin, Dd-BLM caused dsDNA breaks. Significantly, effective cytotoxic concentration of BLM delivered with Dd was 100 times lower than that of free bleomycin.
Stability studies show that Dds can be conveniently stored and transported, and can potentially be used for therapeutic purposes under various climates. Successful BLM delivery by Ad Dds demonstrates that the use of virus like particle (VLP) results in significantly improved drug bioavailability. These experiments open new vistas for delivery of non-permeant labile drugs. |
| doi_str_mv | 10.1371/journal.pone.0005569 |
| format | Article |
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Dodecahedron (Dd) structure is preserved at up to about 50 degrees C at pH 7-8 and during dialysis, freezing and drying in the speed-vac in the presence of 150 mM ammonium sulfate, as well as during lyophilization in the presence of cryoprotectants. The vector is also stable in human serum for 2 h at 37 degrees C. We prepared a Dd-BLM conjugate which upon penetration induced death of transformed cells. Similarly to free bleomycin, Dd-BLM caused dsDNA breaks. Significantly, effective cytotoxic concentration of BLM delivered with Dd was 100 times lower than that of free bleomycin.
Stability studies show that Dds can be conveniently stored and transported, and can potentially be used for therapeutic purposes under various climates. Successful BLM delivery by Ad Dds demonstrates that the use of virus like particle (VLP) results in significantly improved drug bioavailability. These experiments open new vistas for delivery of non-permeant labile drugs.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0005569</identifier><identifier>PMID: 19440379</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adenoviridae - chemistry ; Adenoviridae - genetics ; Adenoviridae - metabolism ; Adenovirus ; Adenoviruses ; Ammonium ; Ammonium sulfate ; Ammonium sulphate ; Antibiotics ; Apoptosis ; Bioavailability ; Biochemistry ; Biophysics ; Bleomycin ; Bleomycin - analogs & derivatives ; Bleomycin - chemistry ; Caffeine ; Cancer ; Cell Biology ; Cell cycle ; Cell growth ; Climate ; Cryoprotectants ; Cryoprotectors ; Cytoplasm ; Cytotoxicity ; Deoxyribonucleic acid ; Dialysis ; DNA ; Dosage and administration ; Drug delivery ; Drug delivery systems ; Drug Delivery Systems - methods ; Drugs ; Electrophoresis, Polyacrylamide Gel ; Fibrosis ; Flow Cytometry ; Freeze drying ; Freezing ; Gene expression ; Genetic vectors ; Genetic Vectors - chemistry ; Genetic Vectors - genetics ; Genetic Vectors - metabolism ; Health aspects ; HeLa Cells ; Heparan sulfate ; Humans ; Lungs ; Microscopy, Atomic Force ; Microscopy, Confocal ; Microscopy, Fluorescence ; Nuclei ; Nuclei (cytology) ; Oncology ; Penetration ; pH effects ; Pneumonitis ; Polyploidy ; Proteins ; Recombinant Proteins - chemistry ; Recombinant Proteins - genetics ; Recombinant Proteins - metabolism ; Respiratory tract diseases ; Senescence ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Sucrose ; Sulfates ; Tethering ; Therapeutic applications ; Toxicity ; Transformed cells ; Tumors ; Ultrasonic imaging ; Vehicles ; Viral proteins ; Viral Proteins - chemistry ; Viral Proteins - genetics ; Viral Proteins - metabolism ; Virology ; Viruses</subject><ispartof>PloS one, 2009-05, Vol.4 (5), p.e5569-e5569</ispartof><rights>COPYRIGHT 2009 Public Library of Science</rights><rights>2009 Zochowska et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Zochowska et al. 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c721t-a1e9fddc246fb15261eadcc1776660cd53fd931c34e2a82e3c34ff7f48d6a6613</citedby><cites>FETCH-LOGICAL-c721t-a1e9fddc246fb15261eadcc1776660cd53fd931c34e2a82e3c34ff7f48d6a6613</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2679213/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2679213/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19440379$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Jagetia, Ganesh Chandra</contributor><creatorcontrib>Zochowska, Monika</creatorcontrib><creatorcontrib>Paca, Agnieszka</creatorcontrib><creatorcontrib>Schoehn, Guy</creatorcontrib><creatorcontrib>Andrieu, Jean-Pierre</creatorcontrib><creatorcontrib>Chroboczek, Jadwiga</creatorcontrib><creatorcontrib>Dublet, Bernard</creatorcontrib><creatorcontrib>Szolajska, Ewa</creatorcontrib><title>Adenovirus dodecahedron, as a drug delivery vector</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Bleomycin (BLM) is an anticancer antibiotic used in many cancer regimens. Its utility is limited by systemic toxicity and dose-dependent pneumonitis able to progress to lung fibrosis. The latter can affect up to nearly 50% of the total patient population, out of which 3% will die. We propose to improve BLM delivery by tethering it to an efficient delivery vector. Adenovirus (Ad) dodecahedron base (DB) is a particulate vector composed of 12 copies of a pentameric viral protein responsible for virus penetration. The vector efficiently penetrates the plasma membrane, is liberated in the cytoplasm and has a propensity to concentrate around the nucleus; up to 300000 particles can be observed in one cell in vitro.
Dodecahedron (Dd) structure is preserved at up to about 50 degrees C at pH 7-8 and during dialysis, freezing and drying in the speed-vac in the presence of 150 mM ammonium sulfate, as well as during lyophilization in the presence of cryoprotectants. The vector is also stable in human serum for 2 h at 37 degrees C. We prepared a Dd-BLM conjugate which upon penetration induced death of transformed cells. Similarly to free bleomycin, Dd-BLM caused dsDNA breaks. Significantly, effective cytotoxic concentration of BLM delivered with Dd was 100 times lower than that of free bleomycin.
Stability studies show that Dds can be conveniently stored and transported, and can potentially be used for therapeutic purposes under various climates. Successful BLM delivery by Ad Dds demonstrates that the use of virus like particle (VLP) results in significantly improved drug bioavailability. These experiments open new vistas for delivery of non-permeant labile drugs.</description><subject>Adenoviridae - chemistry</subject><subject>Adenoviridae - genetics</subject><subject>Adenoviridae - metabolism</subject><subject>Adenovirus</subject><subject>Adenoviruses</subject><subject>Ammonium</subject><subject>Ammonium sulfate</subject><subject>Ammonium sulphate</subject><subject>Antibiotics</subject><subject>Apoptosis</subject><subject>Bioavailability</subject><subject>Biochemistry</subject><subject>Biophysics</subject><subject>Bleomycin</subject><subject>Bleomycin - analogs & derivatives</subject><subject>Bleomycin - chemistry</subject><subject>Caffeine</subject><subject>Cancer</subject><subject>Cell Biology</subject><subject>Cell cycle</subject><subject>Cell growth</subject><subject>Climate</subject><subject>Cryoprotectants</subject><subject>Cryoprotectors</subject><subject>Cytoplasm</subject><subject>Cytotoxicity</subject><subject>Deoxyribonucleic acid</subject><subject>Dialysis</subject><subject>DNA</subject><subject>Dosage and administration</subject><subject>Drug delivery</subject><subject>Drug delivery systems</subject><subject>Drug Delivery Systems - methods</subject><subject>Drugs</subject><subject>Electrophoresis, Polyacrylamide Gel</subject><subject>Fibrosis</subject><subject>Flow Cytometry</subject><subject>Freeze drying</subject><subject>Freezing</subject><subject>Gene expression</subject><subject>Genetic vectors</subject><subject>Genetic Vectors - chemistry</subject><subject>Genetic Vectors - genetics</subject><subject>Genetic Vectors - metabolism</subject><subject>Health aspects</subject><subject>HeLa Cells</subject><subject>Heparan sulfate</subject><subject>Humans</subject><subject>Lungs</subject><subject>Microscopy, Atomic Force</subject><subject>Microscopy, Confocal</subject><subject>Microscopy, Fluorescence</subject><subject>Nuclei</subject><subject>Nuclei (cytology)</subject><subject>Oncology</subject><subject>Penetration</subject><subject>pH effects</subject><subject>Pneumonitis</subject><subject>Polyploidy</subject><subject>Proteins</subject><subject>Recombinant Proteins - chemistry</subject><subject>Recombinant Proteins - genetics</subject><subject>Recombinant Proteins - metabolism</subject><subject>Respiratory tract diseases</subject><subject>Senescence</subject><subject>Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization</subject><subject>Sucrose</subject><subject>Sulfates</subject><subject>Tethering</subject><subject>Therapeutic applications</subject><subject>Toxicity</subject><subject>Transformed cells</subject><subject>Tumors</subject><subject>Ultrasonic imaging</subject><subject>Vehicles</subject><subject>Viral proteins</subject><subject>Viral Proteins - chemistry</subject><subject>Viral Proteins - genetics</subject><subject>Viral Proteins - metabolism</subject><subject>Virology</subject><subject>Viruses</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk1uL1DAUx4so7rr6DUQLwoLgjLk1aV-EYfEysLDg7TWkyUknQ6cZk3Zwv72pU3UqC0oeEk5-538uycmypxgtMRX49dYPoVPtcu87WCKEioJX97JzXFGy4ATR-yfns-xRjNvE0JLzh9kZrhhDVFTnGVkZ6PzBhSHmxhvQagMm-O5VrmKuchOGJjfQugOE2_wAuvfhcfbAqjbCk2m_yL68e_v56sPi-ub9-mp1vdCC4H6hMFTWGE0YtzUuCMegjNZYCM450qag1lQUa8qAqJIATSdrhWWl4YpzTC-y50fdfeujnMqNEpOyIrjggiRifSSMV1u5D26nwq30ysmfBh8aqULvdAtSK1bZFABZVjBa13WFS1wLzTgThaZjtDdTtKHegdHQ9UG1M9H5Tec2svEHSbhI-dAkcDkJBP9tgNjLnYsa2lZ14Icox4SLiqN_ggSl6gvOEvjiL_DuJkxUo1KdrrM-padHSbliguKCJSxRyzuotAzsnE5fyLpknzm8nDkkpofvfaOGGOX608f_Z2--ztnLE3YDqu030bdD73wX5yA7gjr4GAPY32-BkRwn4Fc35DgBcpqA5Pbs9B3_OE1fnv4AFOz-8w</recordid><startdate>20090515</startdate><enddate>20090515</enddate><creator>Zochowska, Monika</creator><creator>Paca, Agnieszka</creator><creator>Schoehn, Guy</creator><creator>Andrieu, Jean-Pierre</creator><creator>Chroboczek, Jadwiga</creator><creator>Dublet, Bernard</creator><creator>Szolajska, Ewa</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20090515</creationdate><title>Adenovirus dodecahedron, as a drug delivery vector</title><author>Zochowska, Monika ; Paca, Agnieszka ; Schoehn, Guy ; Andrieu, Jean-Pierre ; Chroboczek, Jadwiga ; Dublet, Bernard ; Szolajska, Ewa</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c721t-a1e9fddc246fb15261eadcc1776660cd53fd931c34e2a82e3c34ff7f48d6a6613</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Adenoviridae - chemistry</topic><topic>Adenoviridae - genetics</topic><topic>Adenoviridae - metabolism</topic><topic>Adenovirus</topic><topic>Adenoviruses</topic><topic>Ammonium</topic><topic>Ammonium sulfate</topic><topic>Ammonium sulphate</topic><topic>Antibiotics</topic><topic>Apoptosis</topic><topic>Bioavailability</topic><topic>Biochemistry</topic><topic>Biophysics</topic><topic>Bleomycin</topic><topic>Bleomycin - analogs & derivatives</topic><topic>Bleomycin - chemistry</topic><topic>Caffeine</topic><topic>Cancer</topic><topic>Cell Biology</topic><topic>Cell cycle</topic><topic>Cell growth</topic><topic>Climate</topic><topic>Cryoprotectants</topic><topic>Cryoprotectors</topic><topic>Cytoplasm</topic><topic>Cytotoxicity</topic><topic>Deoxyribonucleic acid</topic><topic>Dialysis</topic><topic>DNA</topic><topic>Dosage and administration</topic><topic>Drug delivery</topic><topic>Drug delivery systems</topic><topic>Drug Delivery Systems - methods</topic><topic>Drugs</topic><topic>Electrophoresis, Polyacrylamide Gel</topic><topic>Fibrosis</topic><topic>Flow Cytometry</topic><topic>Freeze drying</topic><topic>Freezing</topic><topic>Gene expression</topic><topic>Genetic vectors</topic><topic>Genetic Vectors - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zochowska, Monika</au><au>Paca, Agnieszka</au><au>Schoehn, Guy</au><au>Andrieu, Jean-Pierre</au><au>Chroboczek, Jadwiga</au><au>Dublet, Bernard</au><au>Szolajska, Ewa</au><au>Jagetia, Ganesh Chandra</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Adenovirus dodecahedron, as a drug delivery vector</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2009-05-15</date><risdate>2009</risdate><volume>4</volume><issue>5</issue><spage>e5569</spage><epage>e5569</epage><pages>e5569-e5569</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Bleomycin (BLM) is an anticancer antibiotic used in many cancer regimens. Its utility is limited by systemic toxicity and dose-dependent pneumonitis able to progress to lung fibrosis. The latter can affect up to nearly 50% of the total patient population, out of which 3% will die. We propose to improve BLM delivery by tethering it to an efficient delivery vector. Adenovirus (Ad) dodecahedron base (DB) is a particulate vector composed of 12 copies of a pentameric viral protein responsible for virus penetration. The vector efficiently penetrates the plasma membrane, is liberated in the cytoplasm and has a propensity to concentrate around the nucleus; up to 300000 particles can be observed in one cell in vitro.
Dodecahedron (Dd) structure is preserved at up to about 50 degrees C at pH 7-8 and during dialysis, freezing and drying in the speed-vac in the presence of 150 mM ammonium sulfate, as well as during lyophilization in the presence of cryoprotectants. The vector is also stable in human serum for 2 h at 37 degrees C. We prepared a Dd-BLM conjugate which upon penetration induced death of transformed cells. Similarly to free bleomycin, Dd-BLM caused dsDNA breaks. Significantly, effective cytotoxic concentration of BLM delivered with Dd was 100 times lower than that of free bleomycin.
Stability studies show that Dds can be conveniently stored and transported, and can potentially be used for therapeutic purposes under various climates. Successful BLM delivery by Ad Dds demonstrates that the use of virus like particle (VLP) results in significantly improved drug bioavailability. These experiments open new vistas for delivery of non-permeant labile drugs.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>19440379</pmid><doi>10.1371/journal.pone.0005569</doi><tpages>e5569</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2009-05, Vol.4 (5), p.e5569-e5569 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1289215672 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adenoviridae - chemistry Adenoviridae - genetics Adenoviridae - metabolism Adenovirus Adenoviruses Ammonium Ammonium sulfate Ammonium sulphate Antibiotics Apoptosis Bioavailability Biochemistry Biophysics Bleomycin Bleomycin - analogs & derivatives Bleomycin - chemistry Caffeine Cancer Cell Biology Cell cycle Cell growth Climate Cryoprotectants Cryoprotectors Cytoplasm Cytotoxicity Deoxyribonucleic acid Dialysis DNA Dosage and administration Drug delivery Drug delivery systems Drug Delivery Systems - methods Drugs Electrophoresis, Polyacrylamide Gel Fibrosis Flow Cytometry Freeze drying Freezing Gene expression Genetic vectors Genetic Vectors - chemistry Genetic Vectors - genetics Genetic Vectors - metabolism Health aspects HeLa Cells Heparan sulfate Humans Lungs Microscopy, Atomic Force Microscopy, Confocal Microscopy, Fluorescence Nuclei Nuclei (cytology) Oncology Penetration pH effects Pneumonitis Polyploidy Proteins Recombinant Proteins - chemistry Recombinant Proteins - genetics Recombinant Proteins - metabolism Respiratory tract diseases Senescence Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Sucrose Sulfates Tethering Therapeutic applications Toxicity Transformed cells Tumors Ultrasonic imaging Vehicles Viral proteins Viral Proteins - chemistry Viral Proteins - genetics Viral Proteins - metabolism Virology Viruses |
| title | Adenovirus dodecahedron, as a drug delivery vector |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-21T10%3A48%3A29IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Adenovirus%20dodecahedron,%20as%20a%20drug%20delivery%20vector&rft.jtitle=PloS%20one&rft.au=Zochowska,%20Monika&rft.date=2009-05-15&rft.volume=4&rft.issue=5&rft.spage=e5569&rft.epage=e5569&rft.pages=e5569-e5569&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0005569&rft_dat=%3Cgale_plos_%3EA473154567%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1289215672&rft_id=info:pmid/19440379&rft_galeid=A473154567&rft_doaj_id=oai_doaj_org_article_ca49f34f0f4543bbb9181b7c46475c31&rfr_iscdi=true |